The first test of intranasal recombinant human interferon-beta ser (IFN-beta ser) as prophylaxis against common colds is reported. IFN-beta ser was cleared from the nose like IFN-alpha. A total of 10 volunteers were each given a total of 2.6 X 10(7) units of IFN-beta ser as 13 doses administered three times daily over 4 days and there were negligible symptoms that were not significantly different from those in 10 given placebo. Twenty-seven volunteers were then given the same regime and challenged after the fourth dose with rhinovirus types 9 and 14. Compared with 27 volunteers given placebo and virus, there were significant reductions in the mean total clinical scores, the amount of nasal secretion, and the frequency of virus excretion. It is concluded that IFN-beta shows antiviral activity in the human respiratory tract and should be tested to determine whether it is tolerated on continued administration.